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Biomedical subjects

J Karnes

Publications and source records attributed to J Karnes.

11 recordsLinked to original sources

Neuropathy Symptom Profile in health, motor neuron disease, diabetic neuropathy, and amyloidosis.

We developed a true-or-false questionnaire with several hundred questions about symptoms encountered in peripheral neuropathy, to be scored by optical reader and computer. Responses were grouped into scales called "Neuropathy," "Weakness," "Sensory," "Autonomic," and subsets of these. Profiles in health were estimated for each scale based on responses from 300 healthy subjects 15 to 65 years old. The sensitivity and specificity of the scales were tested in patients with motor neuron disease, amyloidosis, or diabetes, with or without neuropathy. The questionnaire was useful in detecting neuropathy and staging severity, and in recognizing patterns that may have diagnostic implications.

Adolescent

Peripheral axotomy induces neurofilament decrease, atrophy, demyelination and degeneration of root and fasciculus gracilis fibers.

We have recently shown that peripheral axotomy by hindlimb amputation in adult cats sequentially results in neurofilament and microtubule decrease and axonal atrophy, myelin wrinkling, myelin remodeling (de- and remyelination), more atrophy and axonal degeneration in proximal sciatic and L7 segmental nerve fibers. The neuropathologic, morphometric and teased fiber alterations in the myelinated fibers (MF) of roots and sampled levels of fasciculus gracilis in groups of adult cats 24 months after hindlimb amputation have now been studied. We found: a severe decrease of neurofilaments, axonal atrophy, myelin wrinkling, de- and remyelination and axonal loss in posterior root axons; that these morphologic abnormalities extended up the fasciculus gracilis in the appropriate territories established from degenerative studies; that the retrograde effect was less severe in ventral root fibers, although atrophy and sprouting were demonstrated here, and that the cellular sequence of retrograde atrophic degeneration of ascending axons was similar to that observed in proximal stump axons. These findings confirm that primary afferent neurons are more vulnerable to axotomy than lower motor neurons and may provide an additional explanation for the poorer functional restoration of sensory than of motor deficit after root compression and in delayed nerve reconnection. Our observations also have important implications for interpretation of neuropathologic alterations in roots and fasciculus gracilis, since the observed features may be secondary to axotomy of peripheral nerve fibers induced by disease and not evidence of a primary derangement.

Amputation, Surgical

Capillary number and percentage closed in human diabetic sural nerve.

The number of capillaries per mm2, minimum intercapillary distance, number of endothelial nuclei per capillary section, and percentage of capillaries closed were evaluated in transverse sections of fascicles of 45 control and 36 diabetic sural nerves. All controls and patients were prospectively studied to ascertain their diabetic and neuropathic status. An index of pathology was introduced and it was found to provide a sensitive and reliable measurement of the presence and severity of neuropathy. The number of capillaries and minimum intercapillary distance of diabetic nerves were not significantly different from those of controls (P greater than 0.05). Diabetic nerves exhibited a small but statistically significant increase in the number of endothelial nuclei per capillary that was positively correlated with the severity of neuropathy. The most striking abnormality was the statistically significant increase in the percentage of capillaries closed in patients with neuropathy as compared to those without neuropathy and controls. Among diabetics, this percentage increased with the severity of neuropathy (P = 0.008). The two capillary abnormalities that have been demonstrated may play a role in the development of diabetic polyneuropathy.

Adult

Spatial pattern of nerve fiber abnormality indicative of pathologic mechanism.

Estimates of the number, density, and size distribution of myelinated fibers at selected levels of roots, spinal tracts, and sampled levels of peripheral nerves may be used in the detection and characterization of alterations of motor, sensory, and autonomic neurons and their axons with development, aging and disease. Use of imaging techniques, now available, increases the reliability, versatility, and speed of such analysis. In this study, the authors evaluated the spatial pattern of fibers in sampled frames and contour areas of transverse sections of nerve fascicles, utilizing, the coefficient of variation and index of dispersion (ID), the latter extensively employed by plant ecologists. The ID was used for recognization of increased, normal, or decreased variability of density within fascicles, between fascicles, and between nerves in health and in various experimental neuropathies. In addition, various morphometric measurements were made in transverse sections at defined levels along the hind limb nerves of rats in acute and chronic ischemia, after rhizotomy and in galactose neuropathy. These stereomorphometric studies, emphasizing the number, size, shape, and spatial pattern of fibers, revealed differences among experimental neuropathies and may be found to be helpful in the characterization and prediction of pathologic mechanisms in neuropathies of unknown cause. Specifically, these approaches could be used for study of whether fiber loss in human diabetic neuropathy is multifocal and determination of the levels of such losses.

Acute Disease

Motor neuron disease (ALS): evaluation of detection thresholds of cutaneous sensation.

Cutaneous touch-pressure, vibration, and thermal cooling detection thresholds were estimated on the skin of one foot for 80 patients with motor neuron disease (MND) and compared with that of more than 300 site, age, and sex-matched healthy controls. Fourteen of the patients had elevated thresholds (greater than or equal to 95th percentile): 7 showed elevated thresholds of sensitive points, 5 an increased number of insensitive grid points, and 2 a combination of these criteria. Therefore, raised vibration thresholds occur more frequently in MND patients than in controls (p less than 0.001). A detection threshold abnormality was not demonstrated for touch-pressure or for thermal cooling. These results are in keeping with the demonstrated increased cutaneous myelinated fiber degeneration in this condition and with evidence of sensory neural system involvement at postmortem examination. Although motor neurons are selectively vulnerable in MND, afferent neurons may also be affected, albeit less frequently and/or to a lesser degree.

Adult

The morphometric composition of myelinated fibres by nerve, level and species related to nerve microenvironment and ischaemia.

An extensive morphometric evaluation of the number, density and diameter distribution of myelinated fibres (MFs) of different nerves, of different proximal-distal levels of nerves, and of different species is reported. The methodology used provides reliable estimates of number and size because of the use of optimal histological techniques, semi-thin sections, careful systematic sampling, nonsubjective evaluation of transverse MF profiles using computerized imaging and evaluation of large numbers of MFs and nerves. The non-MF percentage of endoneurial area was also measured as an index of the amount of nerve microenvironment. We have confirmed that the MF composition is quite variable between nerves, between levels of nerves, and between species. In general the density of MFs is lower in the nerves of man than in the nerves of other animals evaluated, in distal than in proximal levels, in old age and in disease. Although increased endoneurial fluid may play a role in resistance to ischaemic block it appears that the intrinsic metabolic properties of the neural tissue itself are most important.

Animals

Introduction of automated systems to evaluate touch-pressure, vibration, and thermal cutaneous sensation in man.

Systems for automatic assessment of cutaneous touch-pressure, vibratory, and thermal sensation have been developed. These systems use stimuli which are quantified and reproducible, a two-alternative forced-choice technique, and programmed steps to test, score, and report. If normal responses from series of healthy persons have been measured, percentile values specific for test, site, age, and sex can be determined. Abnormality, as in neurological disease, can then be defined as the response which has a value greater than that of the 95th (or other) percentile. These systems may be used to detect and validate abnormalities of sensation in neurological disease and in persons at risk from new medications or from industrial toxins, and to monitor worsening or improvement of sensation in follow-up of a patient or in evaluation of therapeutic regimens.

Adult

Computerized image recognition for morphometry of nerve attribute of shape of sampled transverse sections of myelinated fibers which best estimates their average diameter.

A computerized image recognition method was used to measure various attributes of shape of cross-sections of myelinated nerve fibers. Measurements were made at intervals over 1/2 internode of each fiber on 20 fibers from each of 4 sural nerves from rats. Diameters were computed in 6 different ways from the computer measurements and compared for bias, precision, and accuracy between sections and to the diameter of an idealized cylinder reconstructed for each fiber from multiple actual cross sections. The diameter computed from cross-sectional areas of transversely sectioned myelinated fibers, converted into a circle, showed the highest precision, greatest accuracy and least bias. Fibers were classified by shape and the frequency was determined in defined regions (I1 = paranodal, I3= nuclear and I2=region between I1 and I3) of the 1/2 internode. A crenated shape is highly characteristic of the I1 region. The boomerang shape was found most frequently in I3 whereas the circular shape was found most frequently in I2. Epileptical and boomerang shapes of myelinated fibers within fascicles which have been orientated carefully to obtain transverse sections, are not due to obliquity of section. Therefore, using the minor axis to determine the diameter of such profiles, as we had done previously in our laboratory, is in error. We conclude from these studies, that in carefully orientated transverse sections of nerve trucks, the diameter calculated from measurement of area converted to a circular shape is the best among the various estimates of myelinated fiber diameter and is the most suitable one for use in computerized image recognition systems for nerve morphometry. It seems reasonable to extrapolate this general conclusion to myelinated fibers of man.

Animals

Computer assisted sensory examination to detect and quantitate sensory deficit in diabetic neuropathy.

In this report we describe computer assisted systems to evaluate cutaneous sensation to detect raised thresholds of cutaneous sensation. Normative data has been obtained so that thresholds are known for face, hand and foot. Results show that thresholds vary with site, age, and sex. Among more than 100 diabetic patients whose vibratory, touch-pressure and thermal cooling thresholds were evaluated a raised threshold was demonstrated in 49%, 37% and 33%, respectively. This provides helpful knowledge for protocol trials of diabetic neuropathy. Because these approaches provide sensitive and reliable evaluation of deficits of cutaneous sensation not possible with rapid and inexpensive approaches, we suggest that they might find a place in neurotoxin surveillance.

Age Factors